OP0235 DEVELOPMENT AND PRELIMINARY VALIDATION OF THE NOVEL SCLERODERMA CLINICAL TRIALS CONSORTIUM ACTIVITY INDEX
Authors: L. Ross, D. Hansen, S. Proudman, D. Khanna, A. Herrick, W. Stevens, M. Baron, M. Nikpour
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant challenge. Previous activity indices have been criticised for limitations of face and content validity. <h3>Objectives</h3> The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index Working Group to develop a disease activity index (SCTC AI) that has face, content and construct validity. <h3>Methods</h3> Consensus was reached regarding the conceptual definition of disease activity in SSc. All SCTC AI items were required to be measures of the agreed upon construct. See Figure 1 for process of item generation. In all Delphi exercises an <i>a priori</i> threshold of 70% agreement was applied for items to be included or excluded from subsequent rounds. Items that did not meet the threshold for inclusion across 2 survey rounds were omitted. Data from the Australian Scleroderma Cohort Study were used to reduce and weight items. Items were weighted using time dependent Cox proportional hazards regression analysis relative to a combined endpoint of mortality and morbidity (SF 36 physical component score (PCS) below cohort median value). Seven provisional items were not collected in the ASCS. A discrete choice experiment was performed to generate relative weightings for these items. Group based trajectory modelling (GBTM) was used to identify trajectory groups to compare the survival of low vs high disease activity groups using Kaplan Meier survival analyses. Cox proportional hazard modelling was used to evaluate the association between activity scores and mortality, morbidity and SCTC Damage Index (SCTC DI) scores. <h3>Results</h3> The definition of disease activity as agreed by the SCTC AI WG is: <i>Activity in SSc refers to aspects of disease, attributable to SSc, that are potentially reversible, or can be arrested, with time and/or effective therapy. Disease activity may be associated with morbidity and uncontrolled activity may lead to organ dysfunction and mortality.</i> A 24 item index, spanning nine domains of disease was generated with a maximum score of 140 (Table 1). GBTM identified 3 trajectory groups: low activity (n=856 (49%) median baseline SCTC AI score 4 (IQR 0-6)); medium activity (n=745 (42%) median baseline SCTC AI score 10 (IQR 6-14)); high activity (n=164 (9%) median baseline SCTC AI score 16 (IQR 10-22)). There was a graded risk of death associated with increasing activity levels. 4 year survival was poorer in the high disease activity group compared to the low disease activity group (75% vs 95%, p&lt;0.01). Patients with a SCTC AI ≥15.5 had a HR 3.5 (2.26-5.42 p&lt;0.01) for death and greater morbidity was observed in individuals with a SCTC AI ≥9.5 (HR 1.90 (1.61-2.24 p&lt;0.01). There was a significant relationship between SCTC AI scores and worsening damage; HR 4.43 (3.51-5.60, p&lt;0.01) for 1 unit increase of SCTC DI for each unit increase in SCTC AI. <h3>Conclusion</h3> We present a novel outcome measure to quantify the burden of disease activity in SSc. We have employed a rigorous consensus based methodology in combination with data driven methods, to develop an outcome measure that has face, content and criterion validity. Further work is required to externally validate and confirm the construct and discriminative validity of the SCTC AI. <h3>Acknowledgements</h3> This work was supported by Scleroderma Clinical Trials Consortium Working Group Grants and a Betty Z Benedict Award and private philanthropic donations. <h3>Disclosure of Interests</h3> None Declared.